Water → HCID 86610662, compound

HRID 506398Notes

Reaction equation

HRID 506398 reaction equation
[CH2:1]([O:3][C:4]([N:6]1[C:15]2[C:10](=[N:11][C:12](OS(C(F)(F)F)(=O)=O)=[CH:13][CH:14]=2)[C@@H:9]([NH:24][CH:25]([C:40]2[N:45]=[CH:44][C:43]([N:46]3[CH2:51][CH2:50][N:49]([C:52](=[O:54])[CH3:53])[CH2:48][CH2:47]3)=[CH:42][N:41]=2)[C:26]2[CH:31]=[C:30]([C:32]([F:35])([F:34])[F:33])[CH:29]=[C:28]([C:36]([F:39])([F:38])[F:37])[CH:27]=2)[CH2:8][C@H:7]1[CH2:55][CH3:56])=[O:5])[CH3:2].[CH3:57][Al](C)C.O.C(OCC)(=O)C>O1CCOCC1.CCCCCC.C1C=CC([P]([Pd]([P](C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)([P](C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)[P](C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)=CC=1.C(=O)([O-])[O-].[Ag+2].[Cu]Cl>[CH2:1]([O:3][C:4]([N:6]1[C:15]2[C:10](=[N:11][C:12]([CH3:57])=[CH:13][CH:14]=2)[C@@H:9]([NH:24][CH:25]([C:40]2[N:41]=[CH:42][C:43]([N:46]3[CH2:51][CH2:50][N:49]([C:52](=[O:54])[CH3:53])[CH2:48][CH2:47]3)=[CH:44][N:45]=2)[C:26]2[CH:31]=[C:30]([C:32]([F:35])([F:34])[F:33])[CH:29]=[C:28]([C:36]([F:38])([F:39])[F:37])[CH:27]=2)[CH2:8][C@H:7]1[CH2:55][CH3:56])=[O:5])[CH3:2]

Participants

10

Reactant 4

HCID 962WaterHCID 8857Ethyl AcetateHCID 16682925TrimethylaluminumHCID 86610658HCID 86610658, compound

Product 1

HCID 86610662HCID 86610662, compound

Reagents, catalysts & solvents 5

HCID 62652Cuprous chlorideCatalystHCID 178418397HCID 178418397, compoundCatalystHCID 178418647HCID 178418647, compoundCatalystHCID 8058HexaneSolventHCID 312751,4-DioxaneSolvent

Conditions

Temperature
60 °C

Procedure

(2R,4S)-4-{[5-(4-Acetylpiperazin-1-yl)pyrimidin-2-yl]-[3,5-bis-(trifluoromethyl)benzyl]}amino-2-ethyl-6-trifluoromethanesulfonyloxy-3,4-dihydro-2H-[1,5]naphthyridine-1-carboxylic acid ethyl ester (200 mg) is dissolved in 1,4-dioxane (2 ml), and thereto are added dropwise a catalytic amount of tetrakis(triphenylphosphine)palladium, silver carbonate and copper (I) chloride, and a 1M solution (362 μl) of trimethylaluminum in hexane under nitrogen flow. The mixture is stirred at 60° C. for 1 hour. The reaction solution is cooled to room temperature, and thereto are added water and ethyl acetate. The organic layer is washed with saturated brine and dried over magnesium sulfate, then concentrated under reduced pressure. The resulting residue is purified by column chromatography (NH-silica gel; hexane:ethyl acetate=1:2→0:1) to give (2R,4S)-4-{[5-(4-acetylpiperazin-1-yl)pyrimidin-2-yl]-[3,5-bis(trifluoromethyl)benzyl]}amino-2-ethyl-6-methyl-3,4-dihydro-2H-[1,5]naphthyridine-1-carboxylic acid ethyl ester (142 mg). MS (m/z): 694 [M+H]+.

Workup

  1. temperatureThe reaction solution is cooled to room temperature
  2. washThe organic layer is washed with saturated brine
  3. dry with materialdried over magnesium sulfate
  4. concentrationconcentrated under reduced pressure
  5. customThe resulting residue is purified by column chromatography (NH-silica gel; hexane:ethyl acetate=1:2→0:1)

Sources & evidence

ORD record
ord-54ffb0cf9e6743838189e7e809272e46
Source dataset
uspto-grants-2010_08
Patent number
US07781443B2

Reaction notes

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